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Biomedical subjects

P Knight

Publications and source records attributed to P Knight.

16 recordsLinked to original sources

Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model.

STUDY OBJECTIVES: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING: Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS: Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation.

Administration, Intranasal

Evidence that nebulin is a protein-ruler in muscle thin filaments.

Partial amino acid sequence was obtained from the massive myofibrillar protein nebulin. This consists of repeating motifs of about 35 residues and super-repeats of 7 x 35 = 245 residues. The repeat-motifs are likely to be largely alpha-helical and to interact with both actin and tropomyosin in thin filaments. Nebulin from different species was found to vary in size in proportion to filament length. The data are consistent with the proposal that nebulin acts as a protein-ruler to regulate precise thin filament assembly.

Actin Cytoskeleton

Modification of myofibrils by fluorophore-induced photo-oxidation.

The excitation of fluorophores in the vicinity of a myofibril stops both shortening in the presence of ATP and Ca2+, and the extraction of the A-band by NaCl in the presence of Mg pyrophosphate. Shortening is more quickly affected than extraction. These effects can be induced by fluorescently-tagged antibodies bound in the A-band. Both depolymerization of the thick filament and the interaction between the myosin head and actin appear to be modified. Enzymatic lowering of the oxygen concentration in the bathing solution during excitation reduces these effects, indicating that they are due to photo-oxidation catalysed by excitation of the fluorophore. The results suggest that care needs to be exercised to minimize the consequences of these changes on the outcome of fluorescence-based assays of activity. Irradiated myofibrils that do not shorten, hydrolyse ATP at a rate comparable to those that contract, so they may be useful as a model system for the study of crossbridge activity in the ordered array of proteins of the myofibril.

Actins

Permanent junctional reciprocating tachycardia misdiagnosed as 'cardiomyopathy'.

In a nine-year-old female, cardiac failure was erroneously attributed to idiopathic cardiomyopathy and cardiac transplantation was planned. The actual cause of cardiac failure was permanent junctional reciprocating tachycardia (PJRT), a rare form of supraventricular tachycardia. The diagnostic error was discovered before transplantation was performed and the arrhythmia was treated surgically. This resulted in return of near normal cardiac function.

Cardiomyopathies

Effects of position changes on transcutaneous carbon dioxide tension in neonates with respiratory distress.

Routine neonatal care includes frequent position changes. Recent research has concluded that positions other than supine may result in beneficial physiologic responses. Specifically, several studies suggest that neonates may ventilate more effectively in a prone rather than in a supine position. This study tested the hypothesis that transcutaneous carbon dioxide tension (TcPCO2) would be lower in the prone than in the supine position in neonates with respiratory distress. Fourteen ventilated infants were studied. TcPCO2 was measured and recorded in prone, supine, and right-side-lying positions for each subject. There were no statistically significant differences in mean TcPCO2 values between the three positions (F = .45; df 2,39; P = .64). The relationship between TcPCO2 and PaCO2 values was stable (r = .88) during the studies. The results indicate that changing a neonate's position does not significantly alter transcutaneous carbon dioxide tension.

Blood Gas Monitoring, Transcutaneous

Control of infection due to Klebsiella pneumoniae in an intensive care nursery.

Because of an increased incidence of necrotizing enterocolitis (NEC) temporally related to Klebsiella pneumoniae colonization noted in several infants, a study was undertaken to identify the source and to eradicate the infection. Twenty infants in the neonatal intensive care unit (NICU) and 51 in the well-baby nursery were prospectively studied. Cultures were done on all infants. In addition, cultures were done on all employees and parents who regularly visited. Our results showed an increased incidence of infection during this period--8.3% as compared with 4.79% overall. Colonization with K pneumoniae was eradicated, at least temporarily, by establishing a cohort system in both the NICU and the well-baby nursery and by the administration of antibiotics to all infants in these nurseries. Colonized parents and employees were also treated. Follow-up cultures showed clearing of Klebsiella, and the cohort system was abolished. Serotyping of all affected infants later showed that different strains were present, making it unlikely that there was a common source for the Klebsiella. (Initially the source of infection had been thought to be a mother whose premature triplets were colonized. We feel that the eradication of this organism and the subsequent decline in NEC was enhanced by the combination of cohorting and handwashing. The selected use of antibiotics may have prevented an extension of the outbreak, but this could not be proven.

Alabama

Hydrolysis of p-NN'-phenylenebismaleimide and its adducts with cysteine. Implications for cross-linking of proteins.

To understand the extent of the cross-linking of proteins by the bifunctional reagent p-NN'-phenylenebismaleimide, a quantitative study of competing reactions has been undertaken. The two reactive maleimide rings of the bismaleimide are hydrolysed in mildly alkaline aqueous solutions much more rapidly than is the single maleimide ring of the monofunctional analogue N-ethylmaleimide. The kinetics of hydrolysis are second-order, depending on both imide and hydroxyl ion concentration in the pH range 8-10. The hydrolysis of the first imide ring of the bismaleimide is more rapid than the second, with second-order rate constants of 1600 M-1 . s-1 and 500 M-1 . s-1 respectively, at 25 degrees C. The half-times for hydrolysis of the first and second imide rings at pH 9.0 are therefore only 43s and 140s. Because it renders the maleimide ring unreactive towards cysteine, this rapid hydrolysis can limit the extent of cross-linking of proteins by the bismaleimide.

Chemical Phenomena

p-NN'-phenylenebismaleimide, a specific cross-linking agent for F-actin.

Covalent cross-links can be inserted between the subunits of F-actin by using p-NN'-phenylenebismaleimide. Cross-linking reaches its maximum value when one molecule of reagent has reacted with each actin subunit. p-NN'-Phenylenebismaleimide reacts initially with a cysteine residue on one subunit, the slower cross-linking reaction involving a lysine residue on a neighbouring subunit. Hydrolysis of the actin-bound reagent limits the extent of cross-linking. Quantitative analysis of the amounts of cross-linked oligomers seen on polyacrylamide gels containing sodium dodecyl sulphate suggests that neither the binding of the reagent to actin nor the formation of cross-links introduces strain into the structure. The cross-links do not join together different F-actin filaments, and evidence is presented that suggests that the cross-links join subunits of the same long-pitched helix.

Actins

The arm circumference at birth and its relations to other anthropomeric parameters.

The weight, head, chest and arm circumference of four hundred and sixty-one infants in Jamaica were measured during the first twenty-four hours of birth. The purpose of this work was to draw attention to the arm circumference as a possible indicator of the stage of maturity at birth and correlate this parameter against the other three and against factors on the mother. The highest positive correlation was found between the weight and the chest circumference, followed by the weight and arm cirucmference. Attempt to produce an equation to estimate birth weight from arm and chest circumference was unsatisfactory.

Anthropometry

HIV seroprevalence among healthy blood donors in northeastern Zaire.

Human immunodeficiency virus (HIV)-antibody screening of blood donors in northeastern Zaire was reviewed to determine overall seroprevalence in the population and to identify particular subgroups of the population who are at relatively high risk. Six hundred and seventy-five healthy blood donors were tested from March 1989 to May 1990 using either the HIV-CHEK or Karpas cell tests. A total of 25 donors (3.7%) were seropositive, and seropositivity was more common in female donors (5.4%) than in male donors (2.5%, P less than 0.05). Donors who came from major population centres had a higher rate of seropositivity than did individuals coming from rural villages (10.5% vs 2.0%, P less than 0.001). There was a tendency toward increasing seroprevalence during the 13 months of the study with 2.8% of donors positive in 1989 and 5.8% positive in 1990 (P less than 0.1). It is concluded that in healthy blood donors in northeastern Zaire: (1) HIV seropositivity is more frequent in women and in individuals coming from major population centres, and, (2) HIV seropositivity seems to be increasing rapidly.

Blood Donors